DESCRIPTION (Adapted from the application): The diagnosis of AD and most other dementing illnesses can be definitively established only after histological examination of brain tissues and in some cases after biochemical and genetic analyses. The purposes of the neuropathology core are to: 1) provide adequately preserved and well characterized human and animal brain tissue samples for the biochemical and morphometric studies planned in the research projects and for the ongoing research program supported by other grants, 2) identify the neuropathologic changes in the subjects with cognitive and/or neurological deficits and to investigate the presence of pathologic alterations in control subjects, 3) establish number and distribution of selected lesions using morphometric analysis to correlate severity and topography of the lesions with cognitive neurological findings when requested by the investigators, 4) to determine presence, type, and severity of structural lesions in transgenic (Tg) mouse models of AD or other immunohistochemical examinations, and 5) adequately store frozen and fixed tissues for future studies that may be carried out in this and other institutions. Currently, the core stores frozen samples from 368 brains, 232 of which are cases of AD, 92 of other neurodegenerative diseases associated with dementia and 23 controls. Six AD and three cases of frontal-lobe dementia are familial. During the previous five years, the core has examined and stored 86 brains from the Registry cases, 73 of which were AD alone or in combination with other processes. With the partial support from other sources, the core has also acquired and stored 669 brains to confirm or exclude prion diseases or to pursue research projects. Sporadic and familial prion diseases were confirmed in 483 cases. Tissues acquired by the core have been used in 186 publications. The essential role and productivity of the core will be maintained during the next five years.